Advertisement

Tissue Engineering and Regenerative Medicine

, Volume 15, Issue 5, pp 575–590 | Cite as

Biopolymeric In Situ Hydrogels for Tissue Engineering and Bioimaging Applications

  • Adonijah Graham Sontyana
  • Ansuja Pulickal Mathew
  • Ki-Hyun Cho
  • Saji Uthaman
  • In-Kyu Park
Review Article
  • 81 Downloads

Abstract

Background:

Biopolymeric in situ hydrogels play a crucial role in the regenerative repair and replacement of infected or injured tissue. They possess excellent biodegradability and biocompatibility in the biological system, however only a few biopolymeric in situ hydrogels have been approved clinically. Researchers have been investigating new advancements and designs to restore tissue functions and structure, and these studies involve a composite of biometrics, cells and a combination of factors that can repair or regenerate damaged tissue.

Methods:

Injectable hydrogels, cross-linking mechanisms, bioactive materials for injectable hydrogels, clinically applied injectable biopolymeric hydrogels and the bioimaging applications of hydrogels were reviewed.

Results:

This article reviews the different types of biopolymeric injectable hydrogels, their gelation mechanisms, tissue engineering, clinical applications and their various in situ imaging techniques.

Conclusion:

The applications of bioactive injectable hydrogels and their bioimaging are a promising area in tissue engineering and regenerative medicine. There is a high demand for injectable hydrogels for in situ imaging.

Keywords

Bioimaging Biopolymeric injectable hydrogels Gelation 

Notes

Acknowledgements

This work was financially supported by the Basic Science Research Program (No. 2016R1A2B4011184 and 2017R1C1B1003830) and the Bio & Medical Technology Development Program (NRF-2017M3A9E2056374) through the National Research Foundation of Korea (NRF) funded by the Korean government, MSIP. IKP also acknowledges the financial support from a grant (HCRI 17901-22) Chonnam National University Hwasun Hospital Institute for Biomedical Science.

Compliance with ethical standards

Conflicts of interest

The authors have no financial conflicts of interest.

Ethical statement

There are no animal experiments carried out for this article.

References

  1. 1.
    Campoccia D, Doherty P, Radice M, Brun P, Abatangelo G, Williams DF. Semisynthetic resorbable materials from hyaluronan esterification. Biomaterials. 1998;19:2101–27.CrossRefGoogle Scholar
  2. 2.
    Prestwich GD, Marecak DM, Marecek JF, Vercruysse KP, Ziebell MR. Controlled chemical modification of hyaluronic acid: synthesis, applications, and biodegradation of hydrazide derivatives. J Control Release. 1998;53:93–103.CrossRefGoogle Scholar
  3. 3.
    Park KM, Park KD. Injectable hydrogels: properties and applications. In: Chatgilialoglu C, Studer A, editors. Encyclopedia of radicals in chemistry, biology, and materials. 2017.  https://doi.org/10.1002/0471440264.pst663.
  4. 4.
    Hoffman AS. Hydrogels for biomedical applications. Adv Drug Deliv Rev. 2012;64:18–23.CrossRefGoogle Scholar
  5. 5.
    Atala A, Cima LG, Kim W, Paige KT, Vacanti JP, Retik AB, et al. Injectable alginate seeded with chondrocytes as a potential treatment for vesicoureteral reflux. J Urol. 1993;150:745–7.CrossRefGoogle Scholar
  6. 6.
    Westhaus E, Messersmith PB. Triggered release of calcium from lipid vesicles: a bioinspired strategy for rapid gelation of polysaccharide and protein hydrogels. Biomaterials. 2001;22:453–62.CrossRefGoogle Scholar
  7. 7.
    Gulrez S, Al-Assaf S, Phillips G. Hydrogels: methods of preparation, characterisation and applications. In: Carpi A, editor. Progress in molecular and environmental bioengineering - from analysis and modeling to technology applications. In Tech; 2011. p. 117–50.Google Scholar
  8. 8.
    Wu Y, Guo B, Ma PX. Injectable electroactive hydrogels formed via host–guest interactions. ACS Macro Lett. 2014;3:1145–50.CrossRefGoogle Scholar
  9. 9.
    Ma X, Zhao Y. Biomedical applications of supramolecular systems based on host–guest interactions. Chem Rev. 2015;115:7794–839.CrossRefGoogle Scholar
  10. 10.
    Slaughter BV, Khurshid SS, Fisher OZ, Khademhosseini A, Peppas NA. Hydrogels in regenrative medicine. Adv Mater. 2009;21:3307–29.CrossRefGoogle Scholar
  11. 11.
    Kondiah PJ, Choonara YE, Kondiah PP, Marimuthu T, Kumar P, du Toit LC, et al. A review of injectable polymeric hydrogel systems for application in bone tissue engineering. Molecules. 2016;21:E1580.CrossRefGoogle Scholar
  12. 12.
    Deng S, Li X, Yang W, He K, Ye X. Injectable in situ cross-linking hyaluronic acid/carboxymethyl cellulose based hydrogels for drug release. J Biomater Sci Polym Ed. 2018;29:1643–55.CrossRefGoogle Scholar
  13. 13.
    Lu M, Liu Y, Huang YC, Huang CJ, Tsai WB. Fabrication of photo-crosslinkable glycol chitosan hydrogel as a tissue adhesive. Carbohydr Polym. 2018;181:668–74.CrossRefGoogle Scholar
  14. 14.
    Portnov T, Shulimzon TR, Zilberman M. Injectable hydrogel-based scaffolds for tissue engineering applications. Rev Chem Eng. 2017;33:91–107.CrossRefGoogle Scholar
  15. 15.
    Hozumi T, Kageyama T, Ohta S, Fukuda J, Ito T. Injectable hydrogel with slow degradability composed of gelatin and hyaluronic acid cross-linked by Schiff’s base formation. Biomacromolecules. 2018;19:288–97.CrossRefGoogle Scholar
  16. 16.
    Liao J, Jia Y, Wang B, Shi K, Qian Z. Injectable hybrid poly(ε-caprolactone)-b-poly(ethylene glycol)-b-poly(ε-caprolactone) porous microspheres/alginate hydrogel cross-linked by calcium gluconate crystals deposited in the pores of microspheres improved skin wound healing. ACS Biomater Sci Eng. 2018;4:1029–36.CrossRefGoogle Scholar
  17. 17.
    Liu M, Zeng X, Ma C, Yi H, Ali Z, Mou X, et al. Injectable hydrogels for cartilage and bone tissue engineering. Bone Res. 2017;5:17014.CrossRefGoogle Scholar
  18. 18.
    Jain S, Sandhu PS, Malvi R, Gupta B. Cellulose derivatives as thermoresponsive polymer: an overview. J Appl Pharm Sci. 2013;3:139–44.Google Scholar
  19. 19.
    Goes MF, Sinhoreti MA, Consani S, Silva MA. Morphological effect of the type, concentration and etching time of acid solutions on enamel and dentin surfaces. Braz Dent J. 1998;9:3–10.PubMedGoogle Scholar
  20. 20.
    Pillai CKS, Paul W, Sharma CP. Chitin and chitosan polymers: chemistry, solubility and fiber formation. Prog Polym Sci. 2009;34:641–78.CrossRefGoogle Scholar
  21. 21.
    Chen YH, Chung YC, Wang IJ, Young TH. Control of cell attachment on pH-responsive chitosan surface by precise adjustment of medium pH. Biomaterials. 2012;33:1336–42.CrossRefGoogle Scholar
  22. 22.
    Weng L, Le HC, Talaie R, Golzarian J. Bioresorbable hydrogel microspheres for transcatheter embolization: preparation and in vitro evaluation. J Vasc Interv Radiol. 2011;22:1464–1470.e2.CrossRefGoogle Scholar
  23. 23.
    Zhang W, Jin X, Li H, Zhang RR, Wu CW. Injectable and body temperature sensitive hydrogels based on chitosan and hyaluronic acid for pH sensitive drug release. Carbohydr Polym. 2018;186:82–90.CrossRefGoogle Scholar
  24. 24.
    Parenteau-Bareil R, Gauvin R, Berthod F. Collagen-based biomaterials for tissue engineering applications. Materials (Basel). 2010;3:1863–87.CrossRefGoogle Scholar
  25. 25.
    Latifi N, Asgari M, Vali H, Mongeau L. A tissue-mimetic nano-fibrillar hybrid injectable hydrogel for potential soft tissue engineering applications. Sci Rep. 2018;8:1047.CrossRefGoogle Scholar
  26. 26.
    Kawase M, Michibayashi N, Nakashima Y, Kurikawa N, Yagi K, Mizoguchi T. Application of glutaraldehyde-crosslinked chitosan as a scaffold for hepatocyte attachment. Biol Pharm Bull. 1997;20:708–10.CrossRefGoogle Scholar
  27. 27.
    Noah EM, Chen J, Jiao X, Heschel I, Pallua N. Impact of sterilization on the porous design and cell behavior in collagen sponges prepared for tissue engineering. Biomaterials. 2002;23:2855–61.CrossRefGoogle Scholar
  28. 28.
    Geng X, Mo X, Fan L, Yin A, Fang J. Hierarchically designed injectable hydrogel from oxidized dextran, amino gelatin and 4-arm poly(ethylene glycol)-acrylate for tissue engineering application. J Mater Chem. 2012;22:25130–9.CrossRefGoogle Scholar
  29. 29.
    Payne RG, McGonigle JS, Yaszemski MJ, Yasko AW, Mikos AG. Development of an injectable, in situ crosslinkable, degradable polymeric carrier for osteogenic cell populations. Part 2. Viability of encapsulated marrow stromal osteoblasts cultured on crosslinking poly(propylene fumarate). Biomaterials. 2002;23:4373–80.CrossRefGoogle Scholar
  30. 30.
    Burdick JA, Prestwich GD. Hyaluronic acid hydrogels for biomedical applications. Adv Mater. 2011;23:H41–56.CrossRefGoogle Scholar
  31. 31.
    Ma X, Xu T, Chen W, Qin H, Chi B, Ye Z. Injectable hydrogels based on the hyaluronic acid and poly (γ-glutamic acid) for controlled protein delivery. Carbohydr Polym. 2018;179:100–9.CrossRefGoogle Scholar
  32. 32.
    S V, A S, Annapoorna M, R J, Subramania I, Shantikumar V N, et al. Injectable deferoxamine nanoparticles loaded chitosan-hyaluronic acid coacervate hydrogel for therapeutic angiogenesis. Colloids Surf B Biointerfaces. 2018;161:129–38.Google Scholar
  33. 33.
    Han Y, Li Y, Zeng Q, Li H, Peng J, Xu Y, et al. Injectable bioactive akermanite/alginate composite hydrogels for in situ skin tissue engineering. J Mater Chem B. 2017;5:3315–26.CrossRefGoogle Scholar
  34. 34.
    Chan G, Mooney DJ. Ca2+ released from calcium alginate gels can promote inflammatory responses in vitro and in vivo. Acta Biomater. 2013;9:9281–91.CrossRefGoogle Scholar
  35. 35.
    Mumcuoglu D, Fahmy-Garcia S, Ridwan Y, Nicke J, Farrell E, Kluijtmans SG, et al. Injectable BMP-2 delivery system based on collagen-derived microspheres and alginate induced bone formation in a time-and dose-dependent manner. Eur Cell Mater. 2018;35:242–54.CrossRefGoogle Scholar
  36. 36.
    Wang K, Han Z. Injectable hydrogels for ophthalmic applications. J Control Release. 2017;268:212–24.CrossRefGoogle Scholar
  37. 37.
    i-FACTOR™ Peptide enhanced bone graft, Westminster, Colorado USA. 2015. https://www.accessdata.fda.gov/cdrh_docs/pdf14/p140019d.pdf. Accessed 3 Dec 2015.
  38. 38.
    Prathamesh MK, April MK. Injectable hydrogels for cell delivery and tissue regeneration. https://www.sigmaaldrich.com/technical-documents/articles/materials-science/injectable-hydrogels.html. Accessed 1 Apr 2018.
  39. 39.
    Hasan A, Khattab A, Islam MA, Hweij KA, Zeitouny J, Waters R, et al. Injectable hydrogels for cardiac tissue repair after myocardial infarction. Adv Sci (Weinh). 2015;2:1500122.CrossRefGoogle Scholar
  40. 40.
    Bidarra SJ, Barrias CC, Granja PL. Injectable alginate hydrogels for cell delivery in tissue engineering. Acta Biomater. 2014;10:1646–62.CrossRefGoogle Scholar
  41. 41.
    Shalini V, Sarah B, Ho-Man K, Hicham D, David W, Lakshmi S. Evaluation of enzymatically crosslinked injectable glycol chitosan hydrogel. J Mater Chem B. 2015;3:5511–22.CrossRefGoogle Scholar
  42. 42.
    Sealant P. Coseal surgical sealant (CoSeal) 2011. www.accessdata.fda.gov/cdrh_docs/pdf/p010022b.pdf. Accessed 14 Dec 2001.
  43. 43.
    Blake GM, Park-Holohan SJ, Cook GJ, Fogelman I. Quantitative studies of bone with the use of 18F-fluoride and 99mTc-methylene diphosphonate. Semin Nucl Med. 2001;31:28–49.CrossRefGoogle Scholar
  44. 44.
    Xu H, Othman SF, Magin RL. Monitoring tissue engineering using magnetic resonance imaging. J Biosci Bioeng. 2008;106:515–27.CrossRefGoogle Scholar
  45. 45.
    Bakker MH, Tseng CCS, Keizer HM, Seevinck PR, Janssen HM, Van Slochteren FJ, et al. MRI visualization of injectable ureidopyrimidinone hydrogelators by supramolecular contrast agent labeling. Adv Healthc Mater. 2018;7:1701139.CrossRefGoogle Scholar
  46. 46.
    Gudur M, Rao RR, Hsiao Y-S, Peterson AW, Deng CX, Stegemann JP. Noninvasive, quantitative, spatiotemporal characterization of mineralization in three-dimensional collagen hydrogels using high-resolution spectral ultrasound imaging. Tissue Eng Part C Methods. 2012;18:935–46.CrossRefGoogle Scholar
  47. 47.
    Chakravarty R, Hong H, Cai W. Positron emission tomography image-guided drug delivery: current status and future perspectives. Mol Pharm. 2014;11:3777–97.CrossRefGoogle Scholar
  48. 48.
    Lock LL, Li Y, Mao X, Chen H, Staedtke V, Bai R, et al. One-component supramolecular filament hydrogels as theranostic label-free magnetic resonance imaging agents. ACS Nano. 2017;11:797–805.CrossRefGoogle Scholar
  49. 49.
    Ketcham R. X-ray Computer Tomography (CT) 2007. https://serc.carleton.edu/research_education/geochemsheets/techniques/CT.html. Accessed 6 Jun 2018.
  50. 50.
    Weissleder R. Scaling down imaging: molecular mapping of cancer in mice. Nat Rev Cancer. 2002;2:11–8.CrossRefGoogle Scholar
  51. 51.
    Lei K, Ma Q, Yu L, Ding J. Functional biomedical hydrogels for in vivo imaging. J Mater Chem B. 2016;4:7793–812.CrossRefGoogle Scholar
  52. 52.
    Tan J, Fu X, Sun CG, Liu C, Zhang XH, Cui YY, et al. A single CT-guided percutaneous intraosseous injection of thermosensitive simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in ovariectomized minipigs. Osteoporos Int. 2016;27:757–67.CrossRefGoogle Scholar
  53. 53.
    Sivashanmugam A, Charoenlarp P, Deepthi S, Rajendran A, Nair SV, Iseki S, et al. Injectable shear-thinning CaSO4/FGF-18-incorporated Chitin–PLGA hydrogel enhances bone regeneration in mice cranial bone defect model. ACS Appl Mater Interfaces. 2017;9:42639–52.CrossRefGoogle Scholar
  54. 54.
    Piert M, Zittel TT, Becker GA, Jahn M, Stahlschmidt A, Maier G, et al. Assessment of porcine bone metabolism by dynamic [18F]fluoride ion PET: correlation with bone histomorphometry. J Nucl Med. 2001;42:1091–100.PubMedGoogle Scholar
  55. 55.
    Phelps ME, Chatziioannou A, Cherry S, Gambhir S. Molecular imaging of biological processes from microPET in mice to PET in patients. Proc IEEE Int Symp Biomed Imaging. 2002;1–9.Google Scholar
  56. 56.
    Tondera C, Hauser S, Krüger-Genge A, Jung F, Neffe AT, Lendlein A, et al. Gelatin-based hydrogel degradation and tissue interaction in vivo: insights from multimodal preclinical imaging in immunocompetent nude mice. Theranostics. 2016;6:2114–28.CrossRefGoogle Scholar
  57. 57.
    Talukdar Y, Avti P, Sun J, Sitharaman B. Multimodal ultrasound-photoacoustic imaging of tissue engineering scaffolds and blood oxygen saturation in and around the scaffolds. Tissue Eng Part C Methods. 2014;20:440–9.CrossRefGoogle Scholar
  58. 58.
    Yu J, Takanari K, Hong Y, Lee KW, Amoroso NJ, Wang Y, et al. Non-invasive characterization of polyurethane-based tissue constructs in a rat abdominal repair model using high frequency ultrasound elasticity imaging. Biomaterials. 2013;34:2701–9.CrossRefGoogle Scholar
  59. 59.
    Chen Y, Li S, Li X, Zhang Y, Huang Z, Feng Q, et al. Noninvasive evaluation of injectable chitosan/nano-hydroxyapatite/collagen scaffold via ultrasound. J Nanomater. 2012;939821:7.Google Scholar
  60. 60.
    Leferink AM, van Blitterswijk CA, Moroni L. Methods of monitoring cell fate and tissue growth in three-dimensional scaffold-based strategies for in vitro tissue engineering. Tissue Eng Part B Rev. 2016;22:265–83.CrossRefGoogle Scholar
  61. 61.
    McRobbie DW, Moore EA, Graves MJ, Prince MR. MRI from picture to proton. New York: Cambridge University Press; 2006. p. 30–42.Google Scholar
  62. 62.
    Kotecha M, Klatt D, Magin RL. Monitoring cartilage tissue engineering using magnetic resonance spectroscopy, imaging, and elastography. Tissue Eng Part B Rev. 2013;19:470–84.CrossRefGoogle Scholar
  63. 63.
    Xu J, Chen Y, Yue Y, Sun J, Cui L. Reconstruction of epidural fat with engineered adipose tissue from adipose derived stem cells and PLGA in the rabbit dorsal laminectomy model. Biomaterials. 2012;33:6965–73.CrossRefGoogle Scholar
  64. 64.
    Beaumont M, DuVal MG, Loai Y, Farhat WA, Sándor GK, Cheng HLM. Monitoring angiogenesis in soft-tissue engineered constructs for calvarium bone regeneration: an in vivo longitudinal DCE-MRI study. NMR Biomed. 2010;23:48–55.CrossRefGoogle Scholar
  65. 65.
    Bible E, Dell’Acqua F, Solanky B, Balducci A, Crapo PM, Badylak SF, et al. Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by19F- and diffusion-MRI. Biomaterials. 2012;33:2858–71.CrossRefGoogle Scholar
  66. 66.
    Hsueh Y-S, Chen Y-S, Tai H-C, Mestak O, Chao S-C, Chen Y-Y, et al. Laminin-alginate beads as preadipocyte carriers to enhance adipogenesis in vitro and in vivo. Tissue Eng Part A. 2017;23:185–94.CrossRefGoogle Scholar
  67. 67.
    Roeder E, Henrionnet C, Goebel JC, Gambier N, Beuf O, Grenier D, et al. Dose-response of superparamagnetic iron oxide labeling on mesenchymal stem cells chondrogenic differentiation: a multi-scale in vitro study. PLoS ONE. 2014;9:e98451.CrossRefGoogle Scholar
  68. 68.
    Mertens ME, Frese J, Bölükbas DA, Hrdlicka L, Golombek S, Koch S, et al. FMN-coated fluorescent USPIO for cell labeling and non-invasive MR imaging in tissue engineering. Theranostics. 2014;4:1002–13.CrossRefGoogle Scholar
  69. 69.
    Dittmar R, Potier E, van Zandvoort M, Ito K. Assessment of cell viability in three-dimensional scaffolds using cellular auto-fluorescence. Tissue Eng Part C Methods. 2012;18:198–204.CrossRefGoogle Scholar
  70. 70.
    Pan D, Pramanik M, Senpan A, Allen JS, Zhang H, Wickline SA, et al. Molecular photoacoustic imaging of angiogenesis with integrin-targeted gold nanobeacons. FASEB J. 2011;25:875–82.CrossRefGoogle Scholar
  71. 71.
    Cai X, Zhang YS, Xia Y, Wang LV. Photoacoustic microscopy in tissue engineering. Mater Today. 2013;16:67–77.CrossRefGoogle Scholar
  72. 72.
    Liang X, Graf BW, Boppart SA. Imaging engineered tissues using structural and functional optical coherence tomography. J Biophotonics. 2009;2:643–55.CrossRefGoogle Scholar
  73. 73.
    Tondera C, Wieduwild R, Röder E, Werner C, Zhang Y, Pietzsch J. In vivo examination of an injectable hydrogel system crosslinked by peptide-oligosaccharide interaction in immunocompetent nude mice. Adv Funct Mater. 2017;27:1605189.CrossRefGoogle Scholar

Copyright information

© The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biomedical Sciences, Chonnam National UniversityChonnam National University Medical SchoolGwangjuRepublic of Korea
  2. 2.Department of Plastic SurgeryCleveland ClinicClevelandUSA
  3. 3.Department of Polymer Science and EngineeringChungnam National UniversityDaejeonRepublic of Korea

Personalised recommendations